Pharmacokinetics of Controlled Release and Immediate Release Morphine Sulphate Tablets after a Single Dose and Multiple Doses in Chinese Volunteers

健康志愿者１０名，随机交叉口服硫酸吗啡控释片（ＣＲＭＳ）３０ｍｇ（３０ｍｇ×１）和硫酸吗啡普通片（ＩＲＭＳ）２０ｍｇ（１０ｍｇ×２），分别于服药前后各时点取静脉血，用ＧＣＭＳ测定血浆中吗啡含量。以药代软件程序处理，分别求得ＣＲＭＳ和ＩＲＭＳ的Ｃｍａｘ为１９．３８±３．８０和２１．２７±６．２１ｎｇ／ｍｌ；ｔｍａｘ为２．３６±０．３７ｈ和０．５５±０．１６ｈ；ｔ１／２β为３．５３±０．８７ｈ和３．０３±０．７４ｈ，曲线下面积ＡＵＣ为１４５．１５±１７．６５和９３．０８±１６．６５ｎｇ·ｈ／ｍｌ。癌症病人多次口服硫酸吗啡至稳态，ＣＲＭＳ和ＩＲＭＳ的峰浓度分别为２７．４３±０．３３ｎｇ／ｍｌ，２２．６８±０．１６ｎｇ／ｍｌ；谷浓度分别为１９．４５±１．４４ｎｇ／ｍｌ；１８．１４±０．４９ｎｇ／ｍｌ。     

Effects of Diazepam,Phenobarbital,Propranolol,and Cimetidine on Diazepam Oxidizing Isoenzymes in Rat Liver Microsomes

研究地西泮、苯巴比妥、普萘洛尔和西咪替丁对地西泮氧化代谢的影响及其药酶蛋白的初步分析，应用ＨＰＬＣ，ＳＤＳ聚丙烯酰胺凝胶电泳和薄层扫描测定地西泮及其代谢物，并对大鼠肝微粒体和酶蛋白进行分离和含量测定。结果表明地西泮、普萘洛尔和西咪替丁使肝微粒体中Ｐ４５０含量明显降低。地西泮和普萘洛尔明显抑制地西泮Ｃ３羟化活性，大剂量普萘洛尔尚能抑制地西泮Ｎ脱甲基。苯巴比妥明显诱导Ｐ４５０生成，增强地西泮Ｎ脱甲基和Ｃ３羟化酶活性及分子量为５１，０００和５９，０００的电泳蛋白带，而地西泮、普萘洛尔则呈抑制作用。并发现，地西泮Ｎ脱甲基酶活性和分子量为５９，０００蛋白含量呈线性相关（Ｐ＜０．０５），而Ｃ３羟化酶活性则与５１，０００蛋白含量呈线性相关（Ｐ＜０．０１）。因此地西泮Ｃ３羟化代谢可能与５１，０００的Ｐ４５０酶蛋白有关，而Ｎ脱甲基代谢则可能与５９，０００的Ｐ４５０酶蛋白有关。     

PCR扩增IgH基因诊断眼眶良性淋巴增生病的研究

目的；探索某些眼眶良性淋巴星病向恶性淋巴瘤转变的实质。方法；应用聚合酶链反尖（ＰＣＲ）对１８例病理组织学诊断为 眶良性洒巴增生病的石蜡切片进行免疫球蛋白重链（ｇＨ）基因扩增。结果；３例良性淋巴增生病见Ｉ基因一致性重排，电泳产的见一明显的扩增带（１００－１２０ｂｐ），其余１５例未见扩增产物或呈多克隆带。结论；某些良性淋巴增生病的病例存在病理组织学和免疫组织化学不衣检测到的微小单克隆病变。它提示临床为     

Voices from different places: but why a medical school faculty?

Interdisciplinary collaboration between nursing and medicine is a valued goal, but one which is difficult to achieve. Two nurses who are faculty members in medical schools reflect on their unique roles and how these encompass interdisciplinary research, teaching, and practice.     

Distinct autophosphorylation sites sequentially produce autonomy and inhibition of the multifunctional Ca2+/calmodulin-dependent protein kinase

The multifunctional Ca2+/calmodulin-dependent protein kinase (multifunctional CaM kinase) may be an important mediator for neurotransmitters and hormones that utilize Ca2+ as a "second messenger." We examined the ability of autophosphorylation to convert the multifunctional CaM kinase to a Ca2+/calmodulin-independent (autonomous) form to determine whether autophosphorylation is a mechanism for short- or long-term enhancement of Ca2+ action. As the kinase incorporates phosphate during continuous stimulation by Ca2+/calmodulin, its ability to phosphorylate exogenous substrates becomes increasingly autonomous. Withdrawal of Ca2+ after a critical level of phosphate incorporation is reached leads to a "burst" or rapid increase in Ca2+-independent autophosphorylation. The "burst" of autophosphorylation is distinct from the initial Ca2+-dependent autophosphorylation, however, since it inhibits substrate phosphorylation. Both Ca2+-dependent and Ca2+-independent substrate phosphorylation are inhibited by this autonomous autophosphorylation. Thus, autophosphorylation has a dual role in modulating the activity of multifunctional CaM kinase. It initially enables the kinase to continue phosphorylating substrates after Ca2+ levels decline, but it eventually suppresses this autonomous activity. Tryptic phosphopeptide mapping demonstrates that appearance of phosphothreonine-containing peptides is common to several conditions used to generate an autonomous enzyme. Sequencing reveals the critical "autonomy" site to be threonine286. The inhibitory mode of autophosphorylation involves 3 additional phosphopeptides containing a serine and a threonine residue.     

全关节镜下微创复位固定术治疗SandersⅡ、Ⅲ型跟骨关节内骨折的疗效分析

目的 探讨全关节镜下微创复位固定术治疗SandersⅡ、Ⅲ型跟骨关节内骨折的临床疗效。方法 前瞻性随机对照研究。纳入2017年3月—2020年12月徐州仁慈医院足踝外科Sanders Ⅱ、Ⅲ型跟骨骨折患者40例,其中男36例、女4例,年龄18~58（39.6±10.8）岁,左侧22例、右侧18例,Sanders Ⅱ型16例、Ⅲ型24例。40例患者数字表法随机分为关节镜组（采用关节镜下跟骨关节内骨折微创复位、经皮螺钉固定术治疗）、大“L”形切口组（采用传统的大“L”形切口跟骨骨折复位钢板内固定术治疗）,每组20例。观察指标：（1）比较2组患者性别、年龄、体质量指数（BMI）、骨折类型、术前美国足踝外科学协会（AOFAS）踝-后足功能评分等基线资料差异;（2）比较2组患者手术切口长度、手术时间、术中出血量、住院时间、术后切口愈合情况等围术期资料差异;（3）术后观察局部有无麻木感、是否钢板外露、切口皮肤坏死、术后1年是否有创伤性关节炎等手术并发症情况;（4）对比分析2组患者末次随访时AOFAS踝-后足功能评分、Gissnae角和Bohler角。结果 （1）2组患者性别、年龄、BMI、骨折类型、术前AOFAS踝-后足功能评分等基线资料比较,差异均无统计学意义（P值均>0.05）。（2）关节镜组患者的切口长度（0.94±0.08）cm、术中出血量（7.20±1.98）mL、手术时间（41.45±9.96）min、住院时间（8.45±2.01）d,大“L”形切口组患者的切口长度（14.35±1.63）cm、术中出血量（27.35±10.35）mL、手术时间（90.65±12.08）min、住院时间（17.15±6.72）d,关节镜组优于大“L”形切口组,差异均有统计学意义（t=-36.70、-8.54、-14.04、-5.54,P值均<0.001）。（3）术后平均随访12.3个月。术后关节镜组切口均甲级愈合,无创伤性关节炎、足背皮肤麻木。大“L”形切口组20例中,18例患者切口甲级愈合,2例患者切口皮缘坏死、钢板外露,予腓肠神经营养逆行岛状皮瓣修复后伤口愈合;有4例患者术后感足背外侧麻木,经治疗分别于术后8~14个月痊愈。（4）末次随访时AOFAS踝-后足功能评分关节镜组为（92.10±3.16）分、大“L”形切口组为（91.3±2.45）分,术后2组患者跟骨的Gissnae角和Bohler角均在正常范围内,组间比较差异均无统计学意义（P值均>0.05）。结论 与传统的切开复位内固定术相比较,全关节镜下微创手术治疗Sanders Ⅱ、Ⅲ型跟骨关节内骨折,具有手术切口小、手术时间短、内固定牢固、切口愈合好、疗程短、术后瘢痕不明显、功能恢复快等优势。     

Sequence variation within botulinum neurotoxin serotypes impacts antibody binding and neutralization

The botulinum neurotoxins (BoNTs) are category A biothreat agents which have been the focus of intensive efforts to develop vaccines and antibody-based prophylaxis and treatment. Such approaches must take into account the extensive BoNT sequence variability; the seven BoNT serotypes differ by up to 70% at the amino acid level. Here, we have analyzed 49 complete published sequences of BoNTs and show that all toxins also exhibit variability within serotypes ranging between 2.6 and 31.6%. To determine the impact of such sequence differences on immune recognition, we studied the binding and neutralization capacity of six BoNT serotype A (BoNT/A) monoclonal antibodies (MAbs) to BoNT/A1 and BoNT/A2, which differ by 10% at the amino acid level. While all six MAbs bound BoNT/A1 with high affinity, three of the six MAbs showed a marked reduction in binding affinity of 500- to more than 1,000-fold to BoNT/A2 toxin. Binding results predicted in vivo toxin neutralization; MAbs or MAb combinations that potently neutralized A1 toxin but did not bind A2 toxin had minimal neutralizing capacity for A2 toxin. This was most striking for a combination of three binding domain MAbs which together neutralized >40,000 mouse 50% lethal doses (LD(50)s) of A1 toxin but less than 500 LD(50)s of A2 toxin. Combining three MAbs which bound both A1 and A2 toxins potently neutralized both toxins. We conclude that sequence variability exists within all toxin serotypes, and this impacts monoclonal antibody binding and neutralization. Such subtype sequence variability must be accounted for when generating and evaluating diagnostic and therapeutic antibodies.     

双特异性抗体对LAK细胞增殖和细胞毒作用影响的体外研究

将抗ＣＤ３与抗ＨＢｓ的单克隆抗体经化学偶联得到双特异性抗体，观察该双特异性抗体对ＬＡＫ细胞增殖和增强细胞毒性的作用。结果显示双特异性抗体显著提高ＬＡＫ细胞与２．２．１５细胞结合率；促进淋巴细胞增殖。１２５Ｉ－ＵｄＲ释放试验检测发现双特异性抗体增强ＬＡＫ细胞对２．２．１５细胞的细胞毒性且与抗体浓度呈正相关。进一步对抗体的特异性研究表明，加入双特异性抗体后ＬＡＫ细胞对２．２．１５细胞毒性作用显著高于对照组。     

Intact perceptual and conceptual priming in temporal lobe epilepsy: neuroanatomical and methodological implications

Explicit memory appears to be supported by medical temporal lobe structures, whereas separate neocortical regions may mediate perceptual and conceptual implicit memory. Children and adults with temporal lobe epilepsy (TLE) and matched controls were administered experimental verbal memory tests. Performance on implicit tests--word identification and word generation--was contrasted with explicit recognition and recall. Encoding conditions emphasized either conceptual or perceptual aspects of study words and were crossed with presentation modality. The priming performance of participants with TLE did not differ from controls, but participants with TLE did show deficits on recognition and recall measures. Thus, intact left temporal cortex does not appear to be necessary for normal implicit memory performance, even when conceptual processing is emphasized at study or test.     

老年大鼠的海马神经元对微量注射Ach的敏感性

本工作观察了老年大鼠海马神经元对微量注射Ach(10μg/0.5μl)的敏感性。 实验在6只老年大鼠(大于30月龄)和5只年青大鼠(4～5月龄)上进行。结果表明:年青大鼠和老年大鼠的海马神经元对Ach的主要反应模式有所不同,前者多出现神经元放电明显增加的兴奋反应。后者多出现抑制反应,神经元的放电明显减少。此外,老年大鼠的海马神经元对Ach反应的持续时间(包括兴奋和抑制反应)也明显长于年青大鼠。本文对海马神经元敏感性和适应能力的改变可能是影响老年记忆的重要因素进行了讨论。